Antibody Treatment of Marrow Grafts in Vitro: A Principle for Prevention of Graft-versus-Host Disease

Graft-versus-host disease (GvHD) is still a frequent complication in clinical marrow transplantation. It causes severe lesions in several tissues, and it also affects hemopoiesis and the immune response of the recipient. When the major histocompatibility complex (MHC) differ, GvHD is uniformly fatal. A major advance in circumventing GvHD was achieved by selection of histocompatible donors. In 1968, Epstein et al. (4) demonstrated, in dogs, that bone marrow could be grafted successfully from DLAmatched littermates. In man, despite the selection of HLA-matched sibling donors and prophylactic immunosuppressive post-transplant therapy, 50% of the recipients get GvHD and about 25% die from it (27). This mortality was attributed to minor histocompatibility antigens undetected by currently employed in vitro test systems. The limited number of compatible siblings and the occurrence of GvHD in HLA-matched combinations led to experimental studies in which GvHD was suppressed by eliminating the immune-reactive cell population of the graft.